Cancer (malignant neoplasm) is characterized by uncontrolled growth and spread of abnormal cells in a living animal and is one of the leading killer diseases of mankind in history. Each year in the U.S. more than a million people are diagnosed with cancer and half of those people so diagnosed will ultimately die from cancer. Cancer presents itself in human and non-human mammals and kills both.
Massive discovery efforts having been ongoing for years into discovering effective anti-cancer therapies including radiation therapy which can exterminate cancer in some instances and block the spread of cancer in some instances. In that regard, use of laboratory animal models (the use of small animals instead of humans for treatment including testing) and cell cultures are carried out (under accepted and approved protocol and standards) to determine radiation response of tumors and normal organs to an applied dose of radiation.
One present laboratory practice of irradiating animals employs ionizing radiation energy from teletherapy sources (for example, Cobalt-60) or generated x-rays. Such sources are sources which are commonly referred to as external beam radiation and are typically provided by an extended linear accelerator or radioactive source. External beam radiation and external beam radiation therapy is a form of radiation therapy in which the radiation is delivered by a machine pointed at the target area to be radiated and located external to that area, with the source relatively far from i.e. non-local to the patient, animal, or sample (80 cm-100 cm). Modern radiation therapy involving external beam sources include linear accelerators such as those produced by Varian Medical Systems 3100 Hansen Way, Palo Alto, Calif. 94304 USA (such as a Clinac 2300 medical linear accelerator).
During such radiation therapy, it is desired to predict or measure the radiation effect on tumorous tissue and normal organ tissue for the research to be effective. Further, it is desired to measure the extent, biological environmental progression and to measure physiologic quantities relating to the radiation response in small animal tumors, normal organs, or organ systems and so analytical measurements are required.
Presently in some instances radiation is used to therapeutically treat living non-human animals, usually of the order Rodentia, and pets or cattle having cancer, using equipment that is the same or similar to that used on humans. However, the smaller scale size of these animals compared to humans, for example rats and mice, makes the precise irradiation of these animals relatively difficult. Thus it is highly desired to have an apparatus and a method for effectively therapeutically treating animals that is more application selective as to the radiation impacted/targeted tissue locus.
Although currently extremity-implanted tumors can be homogeneously irradiated while shielding the rest of the animal, conformal techniques are desired for evaluating heterogeneous tumor irradiation response, in-situ tumor response, and normal organ response. The use of human-scaled equipment for delivery of conformal techniques remains unacceptable for treating small animals with irradiation.
More particularly in irradiating a small animal such as a mouse or rat, present radiation apparatus provide relatively undesirable large radiation beams to the target small animal. Therefore it is difficult to restrict the radiation distribution to the intended biological system target so that the distribution is well controlled. For example, the application of irradiation to target mouse tumors is difficult without also undesirably irradiating a substantial portion of a normal part of the mouse, causing undesired collateral radiation response effects on the non-desired tissue that obscure the response to the desired tissue tumor irradiation. Similar undesired complications are encountered when irradiating small animals for determining radiation response of their normal organs using present apparatus.
Progress has been more rapid in some areas of research than other areas. For example development of small animal imaging systems, such as micro-positron emission tomography (PET) and micro-computed tomography (CT) and micro-magnetic resonance imaging (MRI) has spawned a flurry of development of imaging agents to measure the extent, biological environment, progression, and response to diseases such as cancer, and to measure physiologic quantities of small animal normal organs or organ systems. However for radiation response, there has not been a similar development that allows one to take advantage of the available impressive imaging resolution. For some members of the small animal classification, such as cell cultures, accurate irradiation using a dose distribution with a controlled variation in intensity and spatial extent is virtually impossible with existing technology. The existing irradiators for small animals are unacceptably cumbersome and may not support the numerous radiation response tests needed.